title: Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1.
abstract: Lymphoid enhancer factor 1 (LEF-1) and T cell factor 1 (TCF-1) are closely related transcription factors that are both expressed during murine T cell differentiation and that regulate the T cell receptor alpha (TCRalpha) enhancer in transfection assays. Targeted gene disruption of either the Tcf1 or Lef1 gene in mice did not affect TCRalpha gene expression and resulted in an incomplete defect or no defect in thymocyte differentiation. Here, we examine a potential redundancy of these transcription factors by analyzing double-mutant mice. In fetal thymic organ cultures from Lef1-/- Tcf1-/- mice, alpha/beta T cell differentiation is completely arrested at the immature CD8+ single-positive (CD8+ ISP) stage and is markedly impaired at an earlier stage. In addition, we find that sorted CD8+ ISP cells from Lef1-/- Tcf1-/- mice express TCRbeta but show a severely reduced level of TCRalpha gene transcription. Together, these data show that LEF-1 and TCF-1 are redundant in the regulation of T cell differentiation and gene expression.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology, University of California, San Francisco 94143-0414, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Okamura
authors.forename: M
authors.initials: M
authors.lastname: Sigvardsson
authors.forename: J
authors.initials: J
authors.lastname: Galceran
authors.forename: S
authors.initials: S
authors.lastname: Verbeek
authors.forename: H
authors.initials: H
authors.lastname: Clevers
authors.forename: R
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D019673:Genes, T-Cell Receptor alpha; D051538:Hepatocyte Nuclear Factor 1-alpha; D051821:Lymphoid Enhancer-Binding Factor 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D009924:Organ Culture Techniques; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; C497574:Lef1 protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D016693:Receptors, Antigen, T-Cell, alpha-beta; D051822:T Cell Transcription Factor 1; D014157:Transcription Factors